Critical Role of Cys168 in Noggin Protein's Biological Function  

作　　者：Wei-DongLIU Xiang-LingFENG Cai-PingREN Jian-LingSHI Xu-YuYANG MingZHAO LiangZHOU KeLAN Kai-TaiYAO 

机构地区：[1]CancerResearchInstitute,CentralSouthUniversity,Changsha410078,China

出　　处：《Acta Biochimica et Biophysica Sinica》2005年第3期181-185,共5页生物化学与生物物理学报（英文版）

基　　金：This work was supported by a grant from Joint Research Scheme Project of National Natural Science Foundation of China and the Hong Kong Research Grants Council(No.39910161994)

摘　　要：Previous studies have indicated that noggin exerts its neural inducing effectby binding and antagonizing bone morphogenetic protein 4 (BMP4).In order to further clarify therelationship between the structure and the function of noggin,and elucidate the possible mechanismresponsible for noggin-BMP4 interaction,we generated three noggin mutants,C168S,C174S and C197S,byusing a site-directed mu-tagenesis method.Ectopic expression of wild-type (WT) noggin,C174S orC197S,in Xenopus animal caps (ACs) by mRNA injection converted the explants (prospective ectoderm)into neural tissue,as indicated by the neural-like morphology and expression of the neural celladhesion molecule (NCAM) in the ACs.In contrast,ACs expressing C168S suffered an epidermal fatesimilar to the control caps.Similarly,among the three mutants,only C168S lost the dorsalizingfunction.These studies highlight the critical role played by Cysl68 in noggin's biologicalactivities.It probably participates in the formation of an intermolecular disulfide bridge.Previous studies have indicated that noggin exerts its neural inducing effectby binding and antagonizing bone morphogenetic protein 4 (BMP4).In order to further clarify therelationship between the structure and the function of noggin,and elucidate the possible mechanismresponsible for noggin-BMP4 interaction,we generated three noggin mutants,C168S,C174S and C197S,byusing a site-directed mu-tagenesis method.Ectopic expression of wild-type (WT) noggin,C174S orC197S,in Xenopus animal caps (ACs) by mRNA injection converted the explants (prospective ectoderm)into neural tissue,as indicated by the neural-like morphology and expression of the neural celladhesion molecule (NCAM) in the ACs.In contrast,ACs expressing C168S suffered an epidermal fatesimilar to the control caps.Similarly,among the three mutants,only C168S lost the dorsalizingfunction.These studies highlight the critical role played by Cysl68 in noggin's biologicalactivities.It probably participates in the formation of an intermolecular disulfide bridge.

关 键 词：NOGGIN site-directed mutagenesis neural induction dorsalizing 

分 类 号：Q51[生物学—生物化学]